Intravitreal Steroid Injections Have Higher Endophthalmitis Risk

Pam Harrison

September 02, 2015

The risk for endophthalmitis after intravitreal steroid injections is almost seven times that seen after injections with anti–vascular endothelial growth factor (VEGF) agents, new research suggests. Clinicians should consider this additional risk when choosing how to best treat individual patients, investigators note.

The study was published online August 14 in Ophthalmology.

"Prior to 2006, the main treatment for several forms of macular edema and even some attempts to treat macular degeneration was steroid injection, but in 2006, ant-VEGF agents just took over, and everyone forgot about steroids and assumed the risk for endophthalmitis was relatively similar between steroids and anti-VEGF agents," lead author Brian VanderBeek, MD, MPH, assistant professor of ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, told Medscape Medical News.

"Now there is a reinterest in steroids because we've got a new preservative-free steroid as well as a sustained-release pellet form for treatment in the eye, and with these new formulations, several groups are trying to push steroid injections as first-line therapy," he added.

"But I believe that whatever the outcomes are, you also need to consider the possible risk associated with treatment, so if there is a difference in the risk of endophthalmitis between the two approaches, this is something that should be factored into the decision as to which of these agents we should be using first to treat the diseases we use these medicines for."

The investigators used the Clinformatics Data Mart Database for the study's analysis. The Clinformatics Data Mart Database is an administrative medical claims database that contains de-identified medical claims of all beneficiaries from a large insurer in the United States.

The researchers aggregated all forms of triamcinolone and dexamethasone available for intravitreal use into the steroid cohort, and all injections of anti-VEGF agents including bevacizumab, ranibizumab, aflibercept, and pegaptanib into the anti-VEGF cohort.

A total of 406,380 intravitreal injections given to 75,249 patients between 2003 and 2012 met inclusion criteria for the study. Of these, 387,714 injections were for anti-VEGF agents and 18,666 injections were for steroids.

Generic triamcinolone accounted for 67.7% of steroid injections, and bevacizumab for 76.6% of the anti-VEGF injections.

Overall, the researchers identified 73 cases (0.02%) of endophthalmitis in the anti-VEGF cohort and 24 (0.13%) cases in the steroid cohort.

On average, cases of endophthalmitis occurred 4.15 days after injection, they add.

After controlling for potential confounders including diagnosis, age, race, and gender, the odds ratio (OR) for endophthalmitis was 6.92 (95% confidence interval [CI], 3.54 - 13.52; P < 0.001) times higher after steroid injection compared with anti-VEGF injections.

Differences Between Cohorts

The steroid injection cohort was significantly younger and had a higher percentage of male and black patients compared with the anti-VEGF cohort (P < .001), the authors observe.

The steroid injection cohort also had a higher percentage of injections associated with diabetic and other diagnosis (P < .001) compared with anti-VEGF agents, which were mostly associated with acute macular degeneration.

However, even though the group makeup between the two cohorts was different, "I controlled for disease-associated reasons for injection," Dr VanderBeek explained.

"So because someone was getting an injection for diabetes, they were not more or less likely to get endophthalmitis compared with someone who was getting an injection for macular degeneration, once you controlled for the medications that were used."

Each year of age slightly decreased the odds of a patient developing endophthalmitis, at an OR of 0.98 (95% CI, 0.97 - 1.00; P = .012), whereas each successive year in which the injection was performed was similarly associated with a decreased risk for endophthalmitis.

For example, an injection done in 2012 was associated with a 14% lower risk for a patient developing this particular complication, at an OR of 0.86 (95% CI, 0.79 - 0.95; P < .001) compared with in 2011.

Furthermore, using diabetes as the comparator group, age-related macular degeneration was associated with a 44% lower risk for endophthalmitis, at an OR of 0.56 (95% CI, 0.33 - 0.92; P = .023), whereas "other" diagnoses had more than twice the risk for endophthalmitis compared with diabetes, at an OR of 2.18 (95% CI, 1.14 - 4.20; P = .019).

"Anti-VEGF agents still don't work for everyone, so there are patients who will benefit from steroid injections either in addition to or in place of anti-VEGF agents," Dr VanderBeek said. "But this study supports the idea that the risk of endophthalmitis is not equal between treatment options and should be factored into therapeutic decision making."

Risks vs Benefits

David Zachs, MD, PhD, professor of ophthalmology, University of Michigan, Ann Arbor, told Medscape Medical News that it is important to know the risks of any procedure, but it is also important to weigh the risk against the benefits.

"We use steroids in situations where they have the opportunity to provide real benefit to patients," Dr Zachs said. "So it means having a discussion with the patient and giving them all the information and all the options they have, but sometimes steroids are what one needs."

For example, some patients, particularly with inflammatory conditions, can benefit from intravitreal steroid injections, as can patients who just do not respond well to the anti-VEGF agents, he added.

"The observations in this study are important because it is the largest sample ever investigated, and it helps sort out a lot of the information in the literature that was conflicting," Dr Zachs said.

"So I think this study really helps settle the issue about the actual rate of endophthalmitis in the real world."

The study was funded by the National Institutes of Health. The authors and Dr Zachs have disclosed no relevant financial relationships.

Ophthalmology. Published online August 14, 2015. Abstract

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